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Targeted Delivery of TGF-β MRNA to Lung Parenchyma Using One-component Ionizable Amphiphilic Janus Dendrimers

Abstract

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle. We deliver an anti-inflammatory cytokine mRNA, transforming growth factor-beta (TGF-β), to produce transient protein expression in the lower regions of the lung. This study highlights IAJD's potential for precise, effective, and safe delivery of TGF-β mRNA to the lung. This delivery system offers a promising approach for targeting therapeutics to the specific tissues, a strategy necessary to fill the current clinical gap in treating parenchymal lung injury and disease.

References
1.
Drzewicka K, Zaslona Z . Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases. Front Immunol. 2024; 15:1328781. PMC: 10973144. DOI: 10.3389/fimmu.2024.1328781. View

2.
Stevenson E, Wilkinson M, Abramova E, Guo C, Gow A . Intratracheal Administration of Acyl Coenzyme A Acyltransferase-1 Inhibitor K-604 Reduces Pulmonary Inflammation Following Bleomycin-Induced Lung Injury. J Pharmacol Exp Ther. 2022; 382(3):356-365. PMC: 9426763. DOI: 10.1124/jpet.122.001284. View

3.
Schrier D, Kunkel R, Phan S . The role of strain variation in murine bleomycin-induced pulmonary fibrosis. Am Rev Respir Dis. 1983; 127(1):63-6. DOI: 10.1164/arrd.1983.127.1.63. View

4.
Chung S, Overstreet J, Li Y, Wang Y, Niu A, Wang S . TGF-β promotes fibrosis after severe acute kidney injury by enhancing renal macrophage infiltration. JCI Insight. 2018; 3(21). PMC: 6238749. DOI: 10.1172/jci.insight.123563. View

5.
Zhang D, Atochina-Vasserman E, Maurya D, Huang N, Xiao Q, Ona N . One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA. J Am Chem Soc. 2021; 143(31):12315-12327. DOI: 10.1021/jacs.1c05813. View